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New Inventions

UW–Madison researchers have identified a new treatment option for a number of macular degenerative diseases including AMD, Stargardt’s disease and juvenile macular dystrophy.

The researchers found that a class of compounds called acid sphingomyelinase inhibitors can be used to fight retinal disorders associated with abnormal accumulations of lipofuscin (a cellular waste product), cholesterol or increased inflammation. One such inhibitor, generic name desipramine, is currently sold on the market as an antidepressant. Other acid sphingomyelinase inhibitors also may be suitable.

UW–Madison researchers and collaborators have identified a potent set of UGM inhibitors that may help fight tuberculosis and other diseases caused by microbial infections. The compounds contain a bicyclic triazolo thiadiazine core with diversified aromatic substituents. They were identified by virtually screening a database of nearly five million commercially available compounds.

The molecules inhibit the growth of microorganisms that depend on UGM to incorporate Galf residues. They also diminish the virulence of pathogenic microorganisms, such as M. tuberculosis, M. smegmatis and Klebsiella pneumonia, that rely on UGM.

UW–Madison researchers have developed a method for treating absence epilepsy with the drug ganaxolone, a synthetic neurosteroid analog that modulates GABAA receptors. The drug has shown promise for treating other forms of epilepsy but has not been recommended for absence epilepsy until now.

The researchers have found that in low doses the drug provides an optimal amount of tonic inhibition that restores function and reduces symptoms in a mouse model. The drug may be particularly useful for treating young patients whose condition is characterized by a reduction in tonic inhibition.

UW–Madison researchers have developed a new cancer treatment that combines a TRAIL receptor agonist with the diabetes drug metformin. Metformin sensitizes even resistant cancer cells to the TRAIL receptor agonists (e.g., lexatumumab) that induce cell death.

Metformin is attractive because its safety has been established over decades in diabetic patients worldwide. As such, there seem to be few barriers to its clinical implementation as a cancer therapeutic in combination with TRAIL receptor agonists. Metformin is commercially available as Glucophage® or in generic form.

UW–Madison researchers have developed a method based on blood lipid chemistry to identify a subject at risk for glucoregulatory dysfunction. The method involves obtaining a biosample from the subject, separating the diacylglycerol fatty acids and determining if the concentration is above or below a control range.

New Patents

UW–Madison researchers have developed an improved design for “dual-slot” antennas that incorporates a cooling sleeve and rigid ceramic tip. The coaxially fed, embedded delivery system focuses energy specifically to the tissue surrounding the antenna tip.

Accommodating long, short or even customized shafts, this flexible design facilitates the practical implementation of antenna technology for clinicians seeking safer, more controlled heating patterns. The heating pattern could be tailored to specific clinical applications that require more spherical or more narrow ablation zones.

UW–Madison researchers have developed a method for growing nanopatterned polymer brushes using SI-ATRP. The method relies on making and using a lithographic mask.

The mask has three layers: a surface, a neutral layer and a block copolymer (BCP) film. The neutral layer serves two purposes. First, it induces the overlying BCP film to form vertical domains. Secondly, it provides initiating sites from which to grow the polymer brush chains.

Before that can happen, parts of the BCP film are selectively removed by etching. This forms a desired pattern of exposed regions. During SI-ATRP, these regions are exposed to a growth solution. The result is a polymer brush made of multiple chains, each of which is attached to the neutral layer.

UW-Madison researchers have developed an improved pretreatment process for robust conversion of biomass. This process, known as Sulfite Pretreatment to Overcome Recalcitrance of Lignocellulose (SPORL), reduces the energy consumption needed for size-reduction processes, required before enzymatic hydrolysis, by more than tenfold. The new method can employ a number of aqueous sulfite or bisulfite solutions over a wide range of pH values and temperatures to weaken the chemical structure of the plant material. It is particularly suitable for woody biomass, softwoods such as pines and other conifers that dominate many forests in the U.S., Canada, Europe and New Zealand, and hardwoods such as poplar, willow and eucalyptus that dominate temperate and boreal forests around the world.

The improved SPORL approach is flexible and integrated easily into current pretreatment systems. The pH of the pretreatment liquor can be adjusted by reagent, making SPORL easily incorporated into current dilute acid approaches to improve the efficiency of the pretreatment. Mechanical size reduction steps such as disk or hammer milling can be implemented directly before or after SPORL depending on the stock material. In addition, the final enzymatic hydrolysis can be coupled directly after the pretreatment with or without washing the material or adding a surfactant to aid in the process. The pretreatment also can be employed with steam explosion, using bisulfite as a catalyst. After pretreatment, the hydrolyzed biomass can be separated and the sugars fermented or catalytically converted into fuels while sulfonated lignin byproducts can be sold to established markets and other wastes burned to produce energy for the process.

The novel SPORL approach is a superior method of biomass pretreatment because of its versatility, simplicity and efficiency. It also has excellent scalability to commercial production. The method will increase the energy efficiency of ethanol fermentation and catalytic fuel production processes through decreased size-reduction energy requirements and maximized enzymatic cellulose conversion in a short period of time. This increase in efficiency will allow biofuels and other bioproducts to become economically competitive with petroleum derived fuels and products.